Frequent breakpoints in the region surrounding FRA3B in sporadic renal cell carcinomas

Viji Shridhar, Liang Wang, Rita Rosati, William Paradee, Ravi Shridhar, Chadwick Mullins, Wael Sakr, David Grignon, Orlando J. Miller, Qi C. Sun, John Petros, David I. Smith

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The constitutive fragile site at chromosomal band 3p14.2, FRA3B, is the most active common fragile site in the human genome. We have localized aphidicolin-induced breakpoints to two distinct clusters, separated by 200 Kb, in FRA3B. Sequence analysis of these regions identified two polymorphic microsatellite markers immediately adjacent to each of these breakpoint clusters. In this report we have used these two new microsatellites and 14 additional 3p microsatellites to analyse chromosome 3p breakage and loss in 94 sporadic RCC samples, including nonpapillary, papillary and oncocytomas. We have found heterozygous loss of 3p14 sequences in > 60% of the RCC samples, including both clear cell and papillary renal carcinomas. We have found frequent breakage in the region immediately surrounding FRA3B, demonstrating that FRA3B does play a role in chromosome breakage and loss in RCC. In contrast to other reports, > 50% of the papillary tumors also showed LOH of 3p markers. We also observed microsatellite instability (MIN) with most of the tested markers in seven of eight oncocytomas and one of 69 clear cell carcinomas. The MIN in some oncocytomas was of the RER+ (replication error) type I phenotype. None of the five 3p14.2 markers detected any homozygous deletions in tumor samples, but 69/94 (73%) of the tumors had LOH for the region, which includes the recently identified FHIT gene.

Original languageEnglish (US)
Pages (from-to)1269-1277
Number of pages9
JournalOncogene
Volume14
Issue number11
DOIs
StatePublished - Jan 1 1997

Keywords

  • Breakpoints
  • Fragile site
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Shridhar, V., Wang, L., Rosati, R., Paradee, W., Shridhar, R., Mullins, C., Sakr, W., Grignon, D., Miller, O. J., Sun, Q. C., Petros, J., & Smith, D. I. (1997). Frequent breakpoints in the region surrounding FRA3B in sporadic renal cell carcinomas. Oncogene, 14(11), 1269-1277. https://doi.org/10.1038/sj.onc.1201100